JP7287427B2 - Cell aspiration support device and control method for cell aspiration support device - Google Patents

Description

TECHNICAL FIELD The present invention relates to a cell aspiration assist device and a control method for the cell aspiration assist device.

In research on biological systems, etc., it is frequently performed to identify characteristic cells from many cells in a cell culture well and to aspirate the cells or their components. For example, in the drug discovery process of discovering or designing a new drug, a drug discovery screening step is performed to search for compounds exhibiting efficacy and activity from among a large number of candidate compounds. In this step, cells exhibiting remarkably specific changes are selected from the cell group in the cell culture wells to which the candidate compound has been given, the cells or cell components are aspirated, and analysis such as mass spectrometry is performed.

When cells are aspirated, for example, a suction pipette with a suction tip or a pipetting device is used, and the cells are aspirated while confirming the cells to be aspirated under a microscope. When aspirating cell components, for example, a fine tip called a nanospray tip is used to aspirate cell components while confirming the cells to be aspirated under a microscope.

In addition to aspirating and analyzing specific cells or cell components in cell culture wells, microscopic images of a large number of cells in cell culture wells are taken and processed to identify individual cells. A cell analysis system has been put into practical use, which identifies each cell and calculates feature quantities such as the size and brightness of each cell in real time.

The cell analysis system can detect characteristic cells and observe changes over time based on the calculated feature amounts. Further, in the cell analysis system, the characteristic amount of each cell is represented by a histogram or a scatter diagram, or displayed as a list.

The process of aspirating cells and cell components involves selecting and aspirating cells to be analyzed while visually inspecting individual cells, which is extremely time-consuming and burdensome for the operator when processing a large number of cells. It was big.
On the other hand, Patent Literature 1 discloses a cell aspiration support system capable of easily detecting candidate cells for analysis from a large amount of cells and immediately aspirating the cells. In the invention described in Patent Document 1, when a confocal image of a sample is acquired and an aspiration point is selected on the acquired image, it is automatically aspirated to the selected position in the xy plane on the XY stage on which the microplate is placed. By moving the tip for suction, suction was performed under the set conditions.

Japanese Patent No. 6066110

Since the main purpose of the conventional cell analysis system was to aspirate a portion of the cells, the aspiration pressure and aspiration time were set to the same conditions in order to ensure the reproducibility of the amount of aspiration. However, since the size and thickness of cells differ for each cell and for each aspiration position, if the aspiration pressure and aspiration time are set to the same conditions in order to achieve reproducibility of the aspiration amount without considering them, In some cases, cells were damaged during aspiration.

SUMMARY OF THE INVENTION It is an object of the present invention to provide a cell aspiration support device and a control method for the cell aspiration support device that can reduce damage to cells.

In order to achieve the above object, the cell aspiration support device (1) according to one aspect of the present invention provides at least one of a tissue, a cell, and a part of a cell housed in a container (a cell culture well plate 3). A tubular aspiration tip (70) for aspirating a sample, an aspiration section (20) for aspirating the sample from the tip of the aspiration tip, an imaging section (103) for imaging the specimen, and an image captured by the imaging section. Information about the height of the sample is detected by focusing on a portion of the sample to be aspirated based on the image obtained, and the height of the tip of the aspiration tip is determined based on the image captured by the imaging unit. Information about the height direction is detected, and the relative position of the suction tip in the height direction with respect to the sample is controlled based on the detected information about the height of the sample and the information about the height direction of the tip of the suction tip. and a control unit (30) for controlling the aspiration chip to aspirate the sample to be aspirated.

Further, in the cell aspiration support device according to the aspect of the present invention, the control unit focuses on the maximum position in the height direction of the sample to be aspirated based on the image captured by the imaging unit. A position lower than a predetermined height may be detected as information relating to the height of the sample.

Further, in the cell aspiration support device according to the aspect of the present invention, the control unit adjusts the height of the aspiration tip to a position a predetermined height lower than the maximum position in the height direction of the sample to be aspirated. It may be controlled.

Further, in the cell aspiration assistance device according to the aspect of the present invention, the control unit detects information about the height of the sample for each aspiration start position at which aspiration is started in the sample or for each sample. can be

Further, in the cell aspiration assisting device according to the aspect of the present invention, when the control unit determines to continue the aspiration work by capturing another image of the sample to be aspirated by the imaging unit, the imaging unit information about the height of the sample is detected by focusing on a portion of the sample to be aspirated based on the image captured by the imaging unit; Information about the height direction of the tip is detected, and based on the detected information about the height of the sample and the information about the height direction of the tip of the suction tip, the relative position of the suction tip in the height direction with respect to the sample. After controlling , the aspiration process for aspirating the sample to be aspirated by the aspiration chip is repeated, and the control unit captures another image of the sample to be aspirated by the imaging unit to continue the aspiration operation. If it is determined not to perform the suction process, the suction process may be terminated.

Further, in the cell aspiration assisting device according to the aspect of the present invention, the control unit converts information on aspiration time and information on aspiration pressure corresponding to the sample to be aspirated based on the image captured by the imaging unit. Accordingly, control may be performed so that the sample to be aspirated is aspirated by the aspiration tip.

Further, in the cell aspiration assisting device according to one aspect of the present invention, an operation unit (35) for selecting whether to automatically or manually aspirate conditions for aspirating the sample to be aspirated; a suction time setting unit (55) for setting the suction time by the suction tip, a suction pressure setting unit (50) for setting the suction pressure by the suction tip, and an image display unit for displaying the image photographed by the photographing unit. wherein, when manually setting conditions for aspirating the sample to be aspirated as a result of operating the operation unit, the control unit stores information indicating the aspiration time set by the aspiration time setting unit. acquires information indicating the suction pressure set by the suction pressure setting unit; and according to the acquired information indicating the suction time and the information indicating the suction pressure, the suction target to be suctioned by the suction tip It may be controlled to aspirate the sample.

Further, in the cell aspiration assisting device according to the aspect of the present invention, the control unit sets information indicating the aspiration time set by the aspiration time setting unit and the aspiration pressure set by the aspiration pressure setting unit. The information to be shown may be stored in association with the sample to be aspirated.

To achieve the above object, a control method for a cell aspiration assisting device according to an aspect of the present invention provides a tubular tube for aspirating a sample that is at least one of a tissue, a cell, and a part of a cell contained in a container. A control method for a cell aspiration assisting device having an aspiration tip and an aspiration section for aspirating the sample from the tip of the aspiration tip, wherein an imaging section images an imaging procedure for imaging the sample, and a control section performs an imaging procedure for the imaging section. a sample height detection procedure for detecting information about the height of the sample by focusing on a portion of the sample to be aspirated based on the image captured by the imaging unit; a tip tip height detection procedure for detecting information about the height direction of the tip of the suction tip based on the obtained image; a relative position control procedure for controlling the relative position of the aspiration tip in the height direction with respect to the sample based on information relating to the aspiration tip; and a control procedure.

Further, in the method for assisting cell aspiration according to an aspect of the present invention, after aspirating the sample, another image is taken to determine whether or not to continue the aspiration operation, and it is determined to continue the aspiration operation. In this case, the imaging procedure, the sample height detection procedure, the tip tip height detection procedure, the relative position control procedure, and the control procedure are performed for each suction start position at which suction is started or for each sample. It may also include steps to take.

According to the present invention, damage to cells can be reduced.

It is a figure which shows the structural example of the cell suction assistance apparatus which concerns on this embodiment. It is a figure which shows an example of the microplate put on the XY stage which concerns on this embodiment, and a cell culture well plate. It is a figure which shows an example of the image which the imaging|photography part image|photographed. FIG. 10 is a diagram showing an example in which the position of the suction tip is shallow with respect to the cells; FIG. 10 is a diagram showing an example in which the position of the suction tip is deep with respect to the cells; FIG. 10 is a diagram showing an example of the optimal position of the suction tip with respect to cells. It is a figure explaining the processing example which acquires the height information of the z-axis direction of the cell which concerns on this embodiment. It is a figure which shows the principle of chip|tip position measurement. It is a figure which shows the relationship between the image observed and a chip|tip position. 4 is a flow chart showing an example of a processing procedure when aspirating a sample according to the present embodiment;

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described with reference to the drawings. In addition, in the drawings used for the following description, the scale of each component etc. is appropriately changed in order to make each component etc. recognizable.

[First embodiment]
FIG. 1 is a diagram showing a configuration example of a cell aspiration support device 1 according to this embodiment. As shown in FIG. 1, the cell aspiration support device 1 includes an image acquisition/analysis unit 10, an aspiration unit 20, a control unit 30, an operation unit 35, an image display unit 40, an aspiration pressure setting unit 50, an aspiration time setting unit 55, It comprises an XYZ stage 60 , suction tip 70 , tip rack 80 and sample rack 90 .

The image acquisition/analysis unit 10 includes a microscopic optical unit 101 , a confocal scanning unit 102 , an imaging unit 103 , a fluorescence light source 104 , a bright field illumination 105 and an XY stage 106 .
The control unit 30 also includes a reception unit 301 , an image acquisition unit 302 , an image processing unit 303 , a storage unit 304 , an operation control unit 305 and a display control unit 306 .

The cell aspiration support device 1 captures images of cells in the cell culture well plate 3 and analyzes the captured images. The cell aspiration assisting device 1 assists aspiration processing of cells or cell components based on the analysis results. In FIG. 1, the plane along which the XY stage 106 moves is defined as the xy plane, and the direction perpendicular to the xy plane is defined as the z-axis direction. Let the left-right direction of the paper surface be the x-axis direction, and the depth direction be the y-axis direction.

The suction tip 70 is, for example, a suction pipette fitted with a suction tip or a nanospray tip, and is used to aspirate cells or cell components.
A plurality of aspiration tips 70 before aspirating cells or cell components are arranged in the tip rack 80 .
A specimen rack 90 stores an aspiration tip 70 that has aspirated cells or cell components. The space in which the sample rack 90 is arranged may be provided with an incubator that keeps the temperature and humidity at predetermined values.

The XYZ stage 60 includes the housing of the cell aspiration support device 1 . The operation of the XYZ stage 60 is controlled under the control of the control section 30 . By driving the XYZ stage 60, the suction unit 20 moves on the xy plane and moves in the z-axis direction.

The suction unit 20 attaches one of the plurality of suction tips 70 stored in the tip rack 80 to the suction unit 20 under the control of the control unit 30 . The suction unit 20 sucks cells or cell components in the cell culture well plate 3 on the microplate 2 placed on the XY stage 106 under the control of the control unit 30 . The aspirator 20 stores the aspirator tip 70 that has aspirated cells or cell components at a predetermined position in the sample rack 90 under the control of the controller 30 . It should be noted that the suction unit 20 moves on the xy plane by moving the XYZ stage 60 and moves in the z-axis direction.

The operation unit 35 is, for example, a touch panel sensor provided on the image display unit 40, a keyboard, mechanical switches, buttons, a mouse, a tablet, and the like. The operation unit 35 detects an operation result of an operation performed by an operator, and outputs operation result information indicating the detection result to the control unit 30 . The operation result information includes information indicating the suction target. For example, the operator sees the image captured by the imaging unit 103 displayed on the image display unit 40, and operates the operation unit 35 to specify the suction target for the image. Further, the operation result information includes an automatic suction instruction for automatically setting the suction conditions or a manual suction instruction for manually setting the suction conditions. Further, the operation result information includes a processing start instruction for instructing the start of processing.

The image display unit 40 displays images captured by the image acquisition/analysis unit 10, analysis results analyzed by the control unit 30, information required for operation input, and the like. The image display unit 40 is, for example, a liquid crystal image display device.

The suction pressure setting unit 50 detects suction pressure information regarding the suction pressure set by the operator and outputs the suction pressure information to the control unit 30 . The suction pressure information includes the pressure before suction, the pressure during suction, and the pressure after suction. The suction pressure setting unit 50 is, for example, a touch panel sensor provided on the image display unit 40, a keyboard, a mechanical switch, a button, a dial, a mouse, a tablet, or the like. Note that the operation unit 35 may also serve as the suction pressure setting unit 50 .

The suction time setting unit 55 detects suction time information regarding the suction time set by the operator and outputs the suction time information to the control unit 30 . The suction time setting unit 55 is, for example, a touch panel sensor provided on the image display unit 40, a keyboard, a mechanical switch, a button, a dial, a mouse, a tablet, or the like. Note that the operation unit 35 may also serve as the suction time setting unit 55 .

Note that the operator operates the suction time setting section 55 and the suction pressure setting section 50 when manually adjusting or setting the suction conditions. Therefore, when automatically setting the suction conditions, the control unit 30 sets the suction time and the suction pressure.

The image acquisition/analysis unit 10 captures an image of the cells in the cell culture well plate 3 on the microplate 2 placed on the XY stage 106 under the control of the control unit 30, and controls the captured image. Output to unit 30 . The image acquisition/analysis unit 10 drives the XY stage 106 under the control of the control unit 30 . Any cell culture vessel may be placed on the XY stage 106, and not limited to the microplate 2, but may be a cell culture dish, a cover glass chamber, a petri dish, or the like.

The microscopic optical unit 101 is an optical system including an objective lens 1011, for example.

The confocal scanning unit 102 includes a confocal optical system and a scanning system. Confocal is an optical system that receives light reflected from the surface of the object to be measured by a detector. , is an optical system designed so that the reflected light is also focused on the detector. In a confocal optical system, for example, light emitted from a point light source is irradiated by an objective lens so as to be condensed at one point on the object to be measured. As the point light source, for example, a laser beam having a specific wavelength and excellent straightness is used. In a confocal optical system, the light reflected by the surface of the object to be measured returns along the same optical path, is separated by a beam splitter or the like, and is focused on a detector. Note that the configuration described above is an example, and is not limited to this.

The imaging unit 103 is, for example, a CCD (Charge Coupled Device) image sensor or a C-MOS (Complementary MOS) image sensor. The photographing unit 103 photographs a specified range on the microplate 2 under the control of the control unit 30 and outputs the photographed image to the control unit 30 .
Note that the imaging unit 103 may include an imaging unit for fluorescence observation and an imaging unit for bright field observation.

The fluorescence light source 104 emits an excitation light beam having a first specific wavelength toward the microplate 2 placed on the XY stage 106 . This causes the excited sample to emit a fluorescence signal with a longer wavelength than the excitation light flux. The fluorescence light source 104 is, for example, an ultra-high pressure mercury lamp, a xenon lamp, an ultraviolet LED (light emitting diode), a laser, or the like, and illuminates the excitation wavelength of the fluorescent substance. The fluorescence light source 104 is used for observation of fluorescence/phosphorescence phenomena from living or non-living samples.

The bright field illumination 105 emits an excitation light beam having a second specific wavelength toward the microplate 2 placed on the XY stage 106 . A bright field illumination 105 is used for bright field observation. The bright field illumination 105 has, for example, an annular shape so as not to interfere with the suction unit 20 during the suction operation.

In the configuration example shown in FIG. 1, a configuration example for confocal two-color fluorescence observation and bright field observation will be described, but the image acquisition/analysis unit 10 is not limited to this configuration. For example, it may be configured with one color of incident fluorescence, with one color of confocal light, or with one color of confocal light and a bright field.

The XY stage 106 moves within the xy plane under the control of the controller 30 . A microplate 2 is placed on the XY stage 106 . Moreover, as shown in FIG. 2, a cell culture well plate 3 is placed on the microplate 2 . FIG. 2 is a diagram showing an example of the microplate 2 and cell culture well plate 3 placed on the XY stage 106 according to this embodiment. The number of wells of the cell culture well plate 3 is 6, 12, 24, 96, for example. Moreover, in the cell culture well plate, for example, there are cases where one or more cells of one type are mounted, and there are cases where cells 4 of several types are mounted. In FIG. 1, reference numeral 4 indicates cells, and reference numeral 5 indicates a cell culture medium (hereinafter also referred to as medium).

The control unit 30 is configured using an information processing device such as a PC (personal computer) including a CPU (central processing unit), a storage device, and the like. The control unit 30 drives the XYZ stage 60 and the suction unit 20 respectively. The control unit 30 controls the microscopic optical unit 101, the confocal scanning unit 102, the imaging unit 103, the fluorescence light source 104, and the luminescence light source 104 so as to capture an image of the designated area in the designated area of the cell culture well plate 3. It controls field illumination 105 and XY stage 106 . The control unit 30 performs image analysis on the captured image, and causes the image display unit 40 to display the analysis result obtained by analyzing the captured image. The control unit 30 determines a sample to be aspirated (at least one of a tissue, a cell, and a part of a cell) according to the result of an operator's investigation of the operation unit 35, and transfers the sample to the microscopic optical unit 101. , the confocal scanning unit 102 , and the XY stage 106 so as to match the optical axes of the imaging unit 103 . The control unit 30 detects height information (in the z-axis direction) for the sample to be aspirated. The control unit 30 detects the height direction of the tip end of the suction tip 70 based on the photographed image, and controls the relative position in the height direction between the sample to be sucked and the tip tip. After controlling the relative positions in the height direction between the sample to be aspirated and the tip of the tip, the control unit 30 performs control to aspirate the sample to be aspirated.
When automatically setting the suction conditions, the control unit 30 automatically sets the suction time and the suction pressure based on the analysis result of the photographed image and performs suction. When the suction condition is manually adjusted or set, the control unit 30 performs suction according to the suction time set by the suction time setting unit 55 and the suction pressure set by the suction pressure setting unit 50 .

The reception unit 301 receives operation result information output by the operation unit 35, suction pressure information output by the suction pressure setting unit 50, and suction time output by the suction time setting unit 55, respectively. The receiving unit 301 outputs the received operation result information, suction pressure information, and suction time to the image processing unit 303 and the operation control unit 305 .

The image acquisition unit 302 acquires an image captured by the imaging unit 103 and outputs the acquired image to the image processing unit 303 . Also, the image acquisition unit 302 causes the storage unit 304 to store the acquired image. The image acquisition unit 302 also outputs the acquired image to the display control unit 306 .

The image processing unit 303 performs image processing on the image acquired by the image acquiring unit 302 . The image processing unit 303 performs various analyzes on the image that has undergone image processing. The image processing unit 303 stores the analysis result in association with the image stored in the storage unit 304 . The image processing unit 303 also outputs the analysis result to the display control unit 306 .
The image processing unit 303, for example, refers to the reference data stored in the storage unit 304 and recognizes the cells/cell organelles in the acquired image by template matching or the like. The image processing unit 303 calculates cell feature amounts such as size, brightness, protein amount, and ion amount for each identified cell. In addition, the image processing unit 303 performs processing such as listing and graphing of information on cells using the calculated characteristic amounts of the cells. The image processing unit 303 outputs, to the image processing unit 303, identification information indicating the identified identification result, the calculated feature amount of the cell, list information of cell-related information, and graphed information. Further, the image processing unit 303 performs, for example, edge detection processing, etc. on the image of the identified cell/organelle region. etc. may be obtained. The image processing unit 303 may output to the image processing unit 303 the obtained cell/cell organelle, central position of the nucleus, peripheral position of the nucleus, and the like.

The storage unit 304 stores reference data in advance. The reference data are images of each of a plurality of cells/organelles or data of feature amounts of the images. A storage unit 304 stores an image captured by the imaging unit 103 . The storage unit 304 stores an image in association with cell feature amounts such as size, brightness, amount of protein, and amount of ions.

The operation control unit 305 uses the central position of the cell/cell organ and the nucleus output by the image processing unit 303, the peripheral position of the nucleus, etc., according to the operation result information that instructs the suction target output by the reception unit 301. By controlling the XY stage 106, the cells to be sucked are moved to the sucking position. The suction position is the center of the xy plane of the suction tip 70 and coincides with the optical axes of the microscopic optical section 101 and the confocal scanning section 102 .
The operation control unit 305 drives the XYZ stage 60 to move the suction unit 20 onto the tip rack 80 in response to the suction processing start instruction output by the reception unit 301 , and attach the suction tip 70 to the suction unit 20 . to control. The operation control unit 305 drives the XYZ stage 60 to move the aspiration chip 70 attached to the aspiration unit 20 to the aspiration position of the cells to be aspirated on the microplate 2 to be processed. In the case of an automatic aspiration instruction, the operation control unit 305 aspirates cells to be aspirated into the aspiration tip 70 based on the aspiration pressure and the aspiration time stored in the storage unit 304 . In the case of a manual aspiration instruction, the operation control unit 305 aspirates cells to be aspirated into the aspiration tip 70 based on the aspiration time information and the aspiration pressure information received by the reception unit 301 . The operation control unit 305 drives the XYZ stage 60 to move the aspiration tip 70 that has aspirated the cells to be aspirated onto the sample rack 90, and controls the aspiration tip 70 to be placed at a predetermined position.

The display control unit 306 causes the image display unit 40 to display the image captured by the imaging unit 103 and output by the image acquisition unit 302 . The display control unit 306 causes the image display unit 40 to display various analysis results output by the image processing unit 303 .

Next, an example of an image captured by the imaging unit 103 will be described.
FIG. 3 is a diagram showing an example of an image captured by the imaging unit 103. As shown in FIG.
In FIG. 3, the region indicated by symbol g1 is an image of cytoplasm, the region indicated by symbol g2 is an image of mitochondria, and the region indicated by symbol g3 is an image of nuclei. The image shown in FIG. 3 is an example of an image of HepG2 cells, which is a cell line derived from human liver cancer. Note that the cells shown in FIG. 3 are only examples, and cells to be aspirated are not limited to these. In addition, the size of cells to be aspirated is, for example, about 50 μm in the case of HeLa cells, which are the first human-derived cell line, and varies greatly depending on the cell type and cell state.

Next, the positional relationship between the cells and the tip of the suction tip 70 will be described with reference to FIGS. 4 to 6. FIG. 4 to 6, one nucleus of the cell culture well plate 3 and the suction tip 70 are enlarged. 4 to 6, reference numeral 41 indicates the nucleus, reference numeral 70a indicates the tip of the suction tip 70 (hereinafter referred to as tip tip 70a), and reference numeral 70b indicates the wall of the suction tip 70. FIG.

First, FIG. 4 will be described.
FIG. 4 shows an example in which the position of the suction tip 70 is shallow with respect to the cells.
In the example shown in FIG. 4, the position of the tip end 70a from the bottom in the z-axis direction is z1. In this case, a gap is generated between the cell 4 and the tip end 70a as indicated by symbol g11. When the nucleus 41 is sucked in such a state, a large amount of medium (cell culture medium) 5 is taken into the suction tip 70 through the gap indicated by symbol g11 during suction. In this way, when a large amount of medium 5 is aspirated, when analysis of cells acquired by the cell aspiration support device is performed by another analysis device, whether the analysis is gene analysis or mass spectrometry, the uptake of medium 5 is analyzed or analyzed. decrease the detection sensitivity of

Next, FIG. 5 will be described.
FIG. 5 is a diagram showing an example in which the suction tip 70 is positioned deep with respect to the cells.
In the example shown in FIG. 5, the position of the tip end 70a from the bottom in the z-axis direction is z2. In this case, since the tip end 70a sticks into the cell 4, the cell may be damaged.

Next, FIG. 6 will be described.
FIG. 6 is a diagram showing an example of the optimum position of the suction tip 70 with respect to cells.
In the example shown in FIG. 5, the position of the tip end 70a from the bottom in the z-axis direction is z3. In this case, the gap between the tip end 70a and the cell 4 is small, and the cell 4 is not penetrated by the tip tip 70a. Thus, in this embodiment, by accurately controlling the z-axis direction of the tip end 70a at the start of aspiration, it is possible to reduce damage to the target during single-cell aspiration.

Next, a process for obtaining height information of cells in the z-axis direction will be described.
FIG. 7 is a diagram illustrating an example of processing for obtaining height information of the cell 4 in the z-axis direction according to this embodiment. FIG. 7A shows an example in which the focal point of the objective lens 1011 coincides with the substantially central position of the cell 4 in the z-axis direction. FIG. 7(b) is an example in which the focal point of the objective lens 1011 coincides with the position of the substantially maximum value of the cell 4 in the z-axis direction.

The motion control unit 305 of the control unit 30 moves the objective lens 1011 of the microscopic optical unit 101 in the z-axis direction. It should be noted that during the process of obtaining the height information of the cell 4 , the suction tip 70 is at the position of the tip rack 80 or is waiting at a sufficiently high position with respect to the cell 4 .
The motion control unit 305 first moves the objective lens 1011 so that the focal point of the objective lens 1011 is on z11 in the z-axis direction, which is the bottom of the cell 4 . This gives the height z11.
Next, the motion control unit 305 moves the objective lens 1011 so that it is focused on z12 in the z-axis direction in FIG. 7A. When the imaging unit 103 performs imaging at the focal position shown in FIG. 7A, an image from which the size of the nucleus 41 can be grasped, for example, can be obtained.
Next, the motion control unit 305 moves the objective lens 1011 so that the focus of the objective lens 1011 is aligned with the substantially maximum position of the cell 4 at z13 in the z-axis direction in FIG. 7(b). This gives the height z13.
The image processing unit 303 obtains height information of the cell 4 using the height z13 and the height z11. Note that the image processing unit 303 may use the height z13 as the height information of the cell 4 .

Next, the outline of the principle of measuring the position of the tip of the suction tip 70 (hereinafter referred to as tip tip 70a) will be described.
FIG. 8 is a diagram showing the principle of chip position measurement. FIG. 8(a) shows a state where the tip end 70a and the objective lens 1011 are focused, and FIG. 8(b) shows a state where the focal point of the objective lens 1011 is within the tip tip 70a. In addition, in FIG. 8, the cells 4 are omitted. FIG. 9 is a diagram showing the relationship between an observed image and chip positions. Also, FIG. 9(a) shows an example of a captured confocal image, and FIG. 9(b) shows the magnitude of contrast in FIG. 9(a). Also, in FIG. 8, the area indicated by reference g101 indicates the first height image and the contrast. The area indicated by symbol g102 shows the image and contrast of the second height higher than the first height. The area indicated by symbol g103 shows the image and contrast of the third height higher than the second height. The area indicated by symbol g104 shows the image and contrast at a fourth height higher than the third height. The area indicated by symbol g105 shows the image and contrast of the fifth height, which is higher than the fourth height.

The objective lens 1011 is moved in the height direction, and the image of the chip tip 70 a is captured by the imaging unit 103 using the bright field illumination 105 . At this time, when a confocal image is acquired while moving the suction tip 70 in the vertical direction (z-axis direction) such as the position shown in FIG. 8A and the position shown in FIG. images of chips with different contrasts are obtained.
When the tip end 70a is positioned at the focal point of the objective lens 1011, as shown in the region g103 in FIG. 9, the highest contrast image is obtained. In this way, the tip end 70a can be detected from the image contrast (see Japanese Patent Laid-Open No. 2016-112012).

In the present embodiment, the positional information of the cell in the height direction described with reference to FIG. 7 and the positional information of the tip end 70a described with reference to FIGS. Controls the position of the tip tip 70a relative to the cell as described. The relative position is, for example, a position lower than the maximum position of the cell by a predetermined height.

Next, an example of a processing procedure for aspirating the cells 4 will be described.
FIG. 10 is a flowchart showing an example of a processing procedure when aspirating a sample according to this embodiment. Note that in FIG. 10, the object to be aspirated is a sample (at least one of tissue, cells, and part of cells).

(Step S<b>1 ) The operator sets the microplate 2 in which cells are cultured at a predetermined position of the cell aspiration support device 1 . At this time, the operator performs fluorescent staining as necessary. Also, the operator places the suction tip 70 on the tip rack 80 according to the purpose of suction. For example, when aspirating cell components, a nanospray tip is placed, and when a single cell is aspirated, a normal suction tip is placed.

(Step S2) The operator operates the operation unit 35 to set the imaging conditions and the like. Subsequently, the reception unit 301 of the control unit receives imaging conditions and the like that are the result of the operation of the operation unit 35 . The imaging conditions and the like include, for example, designation of optical systems such as confocal, incident fluorescence, and phase contrast, wavelength settings, imaging intervals, total imaging time, and the like.

(Step S3) The operator operates the operation unit 35 to set analysis contents and the like. Subsequently, the reception unit 301 of the control unit receives the analysis content or the like that is the result of the operation of the operation unit 35 . Here, the contents of the analysis and the like are, for example, the calculation target of the feature amount of the cell and the detection conditions of the cell of interest. In addition, the feature amount of the cell can be brightness, size, or the like. Moreover, the detection condition is a threshold value of the feature amount or the like. By setting these analysis contents, etc., the control unit 30 automatically detects cells that satisfy the detection conditions.

(Step S4) When the operator manually sets the suction conditions, the operator operates the operation unit 35 to set the suction conditions. Here, the suction conditions are automatic suction instructions that automatically set the suction conditions, manual suction instructions that manually set the suction conditions, pressure before suction, pressure during suction, pressure after suction, suction time, and suction time. actions and the like. Further, the operation during aspiration is, for example, an operation of moving the aspiration tip 70 toward the distal end in the longitudinal direction (z-axis direction) of the aspiration tip at least once after starting the aspiration of the sample. When the operator selects the manual suction instruction, the operator operates the suction pressure setting unit 50 to set the pressure before suction, the pressure during suction, and the pressure after suction. Also, the operator operates the suction time setting unit 55 to set the suction time. Subsequently, the reception unit 301 of the control unit receives the suction condition that is the result of operating the operation unit 35, the suction pressure setting unit 50, and the suction time setting unit 55. FIG. Subsequently, the operation control unit 305 sets suction conditions based on the operation result information received by the receiving unit 301 . When the operation result information is an automatic aspiration instruction, the operation control unit 305 controls the aspiration conditions (pressure before aspiration, pressure before aspiration, pressure during suction, pressure after suction, suction time, operation during suction, etc.) to set suction conditions.

(Step S5) The operator operates the operation unit 35 to set the shooting range. Subsequently, the reception unit 301 of the control unit receives the photographing range as a result of the operation of the operation unit 35 . Note that the imaging range is, for example, one area of the cell culture well plate 3 to be aspirated, which is obtained by dividing the cell culture well plate 3 into a plurality of areas. The operator may operate the operation section 35 to select such a region from the region selection image displayed on the image display section 40 . Alternatively, the control unit 30 may display the captured image on the image display unit 40 after capturing the entire image of the cell culture well plate 3 to be aspirated. In this case, the operator may operate the operation section 35 so as to select a region from the entire image of the cell culture well plate 3 displayed on the image display section 40 .

(Step S6) The operation control unit 305 controls the microscopic optical unit 101, the confocal scanning unit 102, the imaging unit 103, the fluorescence light source 104, the bright field illumination 105, and the XY stage 106 according to the accepted imaging range. The range designated by is photographed under the photographing conditions accepted in step S2. It should be noted that the photographing is performed by photographing continuous still images or moving images at predetermined time intervals.

(Step S7) The image acquisition unit 302 acquires the photographed image. Subsequently, the image processing unit 303 performs image analysis on the acquired image. Note that when the captured image is a moving image, the image acquisition unit 302 acquires the image as a still image at predetermined time intervals. In analysis by image processing, image regions corresponding to cells that satisfy detection conditions are detected.

(Step S8) The display control unit 306 causes the image display unit 40 to display an image based on the result of the image analysis. The display control unit 306 displays the analysis results so that the cells that satisfy the detection conditions are clearly displayed. Note that the display control unit 306 causes the image display unit 40 to display the captured image as a live image in real time.

(Step S9) The operator looks at the image displayed on the image display unit 40, and if there are cells to be aspirated, operates the operation unit 35 to select an image region corresponding to the cells to be aspirated. The image displayed on the image display unit 40 is displayed, for example, by emphasizing the contrast and color so that the cells satisfying the detection conditions are clearly visible. Note that the operator can set a plurality of suction targets for one image. Subsequently, the reception unit 301 determines whether or not a suction target has been designated based on the operation result information output by the operation unit 35 . If the reception unit 301 determines that the suction target has been specified (step S9; YES), it proceeds to the process of step S10, and if it determines that the suction target has been specified (step S9; NO), it returns to the process of step S5. . It should be noted that when returning to the process of step S5, the operator resets the photographing range again. Note that the control unit 30 may automatically generate the suction instruction according to the detection conditions set in step S3. In this case, if there is an image area corresponding to cells that match the detection conditions in the captured image, the control unit 30 may generate an aspiration instruction for each image area of the matching cells.

(Step S10) The operation control unit 305 controls the XY stage 106 based on the image analysis result of the image processing unit 303 to move the aspiration target cell to the aspiration position. The suction position is on the optical axis of the microscopic optical unit 101, for example.

(Step S<b>11 ) The motion control section 305 controls the XYZ stage 60 to move the suction section 20 toward the tip rack 80 and attach a new suction tip 70 to the suction section 20 .

(Step S12) The motion control unit 305 controls the XYZ stage 60 to move the suction unit 20 so that the suction tip 70 matches the suction position on the xy plane. The operation control unit 305 controls the position of the tip end 70a of the suction tip 70 in the z-axis direction to a position sufficiently higher than the cells to be suctioned. Further, at this time, since the bright field illumination 105 has a space in the center, it does not interfere with the suction unit 20 .

(Step S13) Based on the operation result information received by the reception unit 301 in step S4, the operation control unit 305 determines whether or not the suction instruction for the suction target is an automatic suction instruction. If the operation control unit 305 determines that it is an automatic suction instruction (step S13; YES), it proceeds to the process of step S14, and if it determines that it is a manual suction instruction (step S13; NO), it proceeds to the process of step S16. proceed.

(Step S14) At this point, the aspirating target cell and the tip end 70a are vertically overlapped at the aspirating position. However, there are cases where the cells have moved since the time of image acquisition, and there are cases where a specific organ in the cells is targeted for aspiration. In such a case, the reception unit 301 can receive the fine adjustment of the position of the suction unit 20 or the microplate 2 as an operation result of the operation of the operation unit 35 by the operator. In fine adjustment of the position, a photographed image can be displayed on the image display section 40 in real time, and a movement instruction can be received from the operator via the operation section 35 . At this time, it is desirable to apply a fluorescent material to the tip end 70a of the suction tip 70 so that the position of the suction tip 70 can be grasped even from the fluorescence observation image. Alternatively, the suction tip 70 may be visualized by providing an LED light source near the tip mounting portion of the suction portion 20 and irradiating the tip direction of the suction tip 70 with light of a predetermined wavelength. After processing, the control unit 30 proceeds to the treatment of step S15.

(Step S15) After the fine adjustment of the position is completed, the motion control unit 305 scans the objective lens 1011 in the z-axis direction so as to obtain the information in the height direction of the cell 4, as described with reference to FIG. to shoot. Subsequently, after focusing the objective lens 1011 on the maximum position of the cells to be inhaled (for example, z13 in FIG. 7B), the operation control unit 305 drives the suction unit 20 to move the suction tip 70 in the z-axis direction. It is driven to lower it to bring it closer to the cell. At this time, the image processing unit 303 analyzes the captured image and detects the height of the tip end 70a. Subsequently, based on the height information of the tip tip 70a detected by the image processing unit 303, the operation control unit 305 moves the tip tip 70a to a position lower than the maximum position of the cell 4 by a predetermined height (for example, see FIG. 6). The suction unit 20 is driven so as to lower the suction tip 70 in the z-axis direction. The operation control unit 305 may associate the aspiration start position finely adjusted in this way with the cells to be aspirated, and store them in the storage unit 304 for learning. Note that the operation control unit 305 stores information indicating the relative position between the cell 4, which is the suction start position at which suction is started, and the tip end 70a, or information indicating the relative position after fine adjustment, in the storage unit 304. You may make it learn by making it memorize|store in connection with the information which shows.

(Step S16) The operation control unit 305 executes cell aspiration. At this time, the operation control unit 305 captures images before and after cell aspiration. Subsequently, the display control unit 306 causes the image display unit 40 to display the captured image. This makes it possible to confirm the certainty of the suction work even after the fact. The operator adjusts the pressure before suction, the pressure during suction, the pressure after suction, and the suction time while viewing the live image displayed on the image display unit 40 . Note that the operation control unit 305 may associate the set aspiration time and aspiration pressure with the cells to be aspirated and store them in the storage unit 304 for learning. Note that the operation control unit 305 may capture images captured before, during, and after suction. After processing, the control unit 30 proceeds to the treatment of step S17.

(Step S17) After aspirating the cells, the operation control unit 305 controls the XYZ stage 60 to move the aspirating unit 20 in the direction of the sample rack 90 and release the aspirating tip 70 from which the cells have been aspirated. store it. Subsequently, the operation control unit 305 causes the storage unit 304 to store the image captured during the aspiration work in association with the aspiration tip 70 from which the cells have been aspirated. Note that the suction tip 70 is provided with an identifiable identifier. Further, the operation control unit 305 may cause the storage unit 304 to store images captured before, during and after aspiration in association with the aspirated sample (specimen, specimen). This can improve the certainty of the analysis.

(Step S18) The operation control unit 305 determines whether or not an instruction to aspirate other cells in the image captured in step S6 has been issued in step S9. When the operation control unit 305 determines that an aspiration instruction for another cell is being issued, that is, there is another aspiration target (step S18; YES), the operation control unit 305 returns to the process of step S10. When the operation control unit 305 determines that no other cells have been instructed to aspirate, that is, there is no other aspiration target (step S18; NO), the process proceeds to step S19.

(Step S19) The operator looks at the operation selection screen displayed on the image display unit 40, and operates the operation unit 35 to determine whether or not to continue the suction operation by photographing moving images and other images. select. Subsequently, the reception unit 301 receives operation result information output by the operation unit 35 . Subsequently, based on the operation result information received by the receiving unit 301, the operation control unit 305 determines whether or not to continue the suction work by capturing another image. If the operation control unit 305 determines to continue the suction work by capturing another image (step S19; YES), the operation control unit 305 returns to the process of step S5, and repeats the processes of steps S5 to S19. If the operation control unit 305 determines not to continue the suction work by capturing another image (step S19; NO), the suction process ends.

In addition, although the example mentioned above demonstrated the example which finely adjusts the position of the suction part 20 or the microplate 2 by step S14, it is not restricted to this. The operator may finely adjust the height of the tip end 70 a while viewing the live image displayed on the image display section 40 . The operation control unit 305 controls, for example, the suction tip 70 to descend from above the cell according to the result of the operation of the operation unit 35 by the operator, and changes in the shape of the cell when the tip contacts the cell. may be detected to finely adjust the suction start position. Note that the operation control unit 305 may associate the finely adjusted aspiration start position in the z-axis direction with the cells to be aspirated, and store them in the storage unit 304 for learning.

The fine adjustment performed in step S14 is not limited to the fine adjustment of the position, and may be the suction pressure or the suction time. In this case, the operator refers to, for example, the image when the previous cell was aspirated, and determines the pressure before aspiration, the pressure during aspiration, the pressure after aspiration, and the aspiration time automatically set by the control unit 30. At least one of them may be set by operating at least one of the operation section 35 , the suction pressure setting section 50 and the suction time setting section 55 . In this case as well, the operation control unit 305 may associate the finely adjusted suction pressure and suction time with the cells to be sucked, and store them in the storage unit 304 for learning.

After the suction conditions are stored in the storage unit 304 in step S16, if another suction target is specified, the control unit 30 restores the stored suction conditions to the initial values at the next manual suction instruction. may be used.

In the example described with reference to FIG. 6 and the like, for example, the approximate center of the nucleus 41 of the cell 4 is aligned with the optical axis of the objective lens 1011 and the center of the suction tip 70, but the present invention is not limited to this. . When the position to aspirate the nucleus of the cell is specified, the operation control unit 305 moves the XY stage 106 so that the approximate center of the nucleus 41 coincides with the optical axis of the objective lens 1011 and the center of the aspiration tip 70 as described above. Control. When the side of the nucleus of the cell is specified as the position to be aspirated, the motion control unit 305 controls the XY stage 106 so that the side of the nucleus is aligned with the optical axis of the objective lens 1011 and the center of the suction tip 70. You may do so. The control unit 30 may control the XY stage 106 to a position where the nucleus of a specific cell is arranged inside the wall of the suction tip 70, for example. Alternatively, the controller 30 may control the XY stage 106 so that the tip of the wall of the suction tip 70 contacts the cell wall of the specific cell. In this manner, the motion control unit 305 may control the XY stage 106 so as to align the suction point with the optical axis in accordance with the operator's instruction.

Thus, according to the present embodiment, the control unit 30 can control the XY stage 106 to accurately set the xy direction for cells to be aspirated designated by the operator. As a result, according to the present embodiment, cells to be aspirated can be aspirated without damaging cells surrounding the cells to be aspirated. It is very important for single-cell gene analysis not to damage surrounding cells. If the cells surrounding the aspirated cell are damaged, there is a risk that the cell will die and spread its own gene fragments around. According to this embodiment, since adjustment is performed in the z-axis direction, it is possible to avoid contamination in which gene fragments enter the aspiration tip 70 that has aspirated the cells to be aspirated via the culture medium.

In addition, although the example mentioned above demonstrated the example which an operator sets both suction time and suction pressure when setting a suction condition manually, it is not restricted to this. The operator may set at least one of the suction time and the suction pressure. In this case, the control unit 30 may refer to information stored in the storage unit 304 to set items that have not been set based on the result of the image analysis.

As described above, in the present embodiment, positional information of a sample (at least one of a tissue, a cell, and a part of a cell) in the height direction and tip tip 70a (for example, 4) is detected. In this embodiment, the relative position of the tip end 70a with respect to the sample is controlled using the detected positional information of the sample in the height direction and the positional information of the tip end 70a. In this embodiment, the sample is aspirated after controlling the relative position of the tip end 70a with respect to the sample.

With this configuration, according to the present embodiment, suction is performed after controlling the relative position of the tip end 70a with respect to the sample, so damage to cells can be reduced. That is, according to the present embodiment, it is possible to prevent the cells from being damaged by piercing the cells with the tip end 70a too deeply. In addition, according to this embodiment, it is possible to prevent a large amount of culture medium from being taken into the tip during aspiration due to a gap between the tip tip 70a and the cells due to too shallow aiming in the z-axis direction. . As a result, according to this embodiment, regardless of whether the analysis is genetic analysis or mass spectrometry, incorporation of the culture medium can prevent a decrease in detection sensitivity in the latter stage.
As described above, according to the present embodiment, it is possible to reduce the damage to the obtained cells and to reduce the contamination of the culture medium, which is a hindrance to the analysis. That is, according to this embodiment, it is possible to obtain a sample suitable for genetic analysis of cells.

Further, in this embodiment, the suction conditions (suction time, suction pressure) can be manually set. Thereby, the operator can confirm the state of the cells by the live image displayed on the image display unit 40, or operate the aspiration conditions while confirming the conditions to instruct to aspirate the sample. As described above, in the present embodiment, even when an instruction is given to automatically set the suction conditions, the operator can finely adjust the suction conditions by operating the operation unit 35, for example. made it possible. As a result, according to the present embodiment, whether the suction conditions are set automatically or manually, there is little damage to the obtained cells, and the medium that is detrimental to the analysis contamination can be reduced.

In addition, in the present embodiment, the manually set aspiration conditions, the finely adjusted aspiration conditions, and the relative position between the cell and the tip of the tip are associated with the cell and stored in the storage unit 304 for learning. made it Thus, according to the present embodiment, each cell can be aspirated using the optimum aspiration condition and the relative position between the cell and the tip of the tip.

Further, according to the present embodiment, when the cell aspiration assisting device 1 has an incubator function, it is possible to perform a test corresponding to changes over time. For example, using a time-lapse imaging function and an image analysis function that perform continuous imaging at predetermined time intervals, it is also possible to capture changes in cells after reagent addition and automatically perform aspiration.

In addition, in the conventional technology, since it is assumed that a certain amount of a part of cells is collected and subjected to mass spectrometry, in most cases, the specifications are such that the suction pressure and the suction time are kept constant and the suction is performed. . On the other hand, in this embodiment, for example, it is assumed that a whole cell or a plurality of cells are aspirated for genetic analysis. Therefore, in this embodiment, the operator can easily set the suction pressure and the suction time manually in addition to the automatic setting of the suction conditions. As a result, according to the present embodiment, suction can be performed in accordance with the purpose of experiments and analyses.

In addition, according to this embodiment, when acquiring cells, it is possible to manually set the aspiration conditions suitable for individual cells, the height in the z-axis direction at the start of aspiration, the xy direction, and the like. According to the present embodiment, with the function of manually setting the approach of the suction tip 70 to the cell, the pressure of suction, the suction time, the timing of pulling up the suction tip 70 from the cell, etc. can all be performed while checking the live image. It can be set and adjusted by the operator. According to this embodiment, with this function, for example, when the cells cannot be completely aspirated, the operator changes the aspiration pressure so that the pressure is applied until all the cells are aspirated into the aspiration tip 70.・It can be adjusted. Further, according to this embodiment, it is possible to aspirate a plurality of cells using one aspiration tip 70 depending on the purpose.

<Modification/Application>
Modifications and application examples of the present embodiment will be described below.
For example, the control unit 30 performs label-free image analysis in combination with pattern recognition technology. In this case, image data is stored in the storage unit 304 in advance, and the control unit 30 refers to the image data stored in the storage unit 304 to perform pattern recognition on cells, for example. Thus, according to the modification/application example, sampling can be performed with less stress applied to the cells.

Also, a container (for example, a tube) is prepared in the sample rack 90 or the microplate 2, and the control unit 30 controls the aspirated sample (specimen) to be discharged into the container, so that it can be brought into the subsequent analysis. can make it easier to do. In addition, the control unit 30 uses one aspiration tip 70 to collect a sample in a 1-well plate for each aspiration, recovers a sample in a 1-well plate after a plurality of aspirations, and uses a plurality of aspiration tips 70. The collection method may be controlled depending on the application, such as collecting the sample in a 1-well plate.
For example, by acquiring characteristic samples and aggregating these samples, according to the modification/application example, it is possible to detect a sample, which is a target that could only be detected in minute amounts in the past.

Further, for example, by placing a reagent in the container in advance, the sample in the suction tip 70 can be eluted according to the modified example/application example.
Further, the control unit 30 drives the tip of the suction tip 70, for example, to hit the wall of the container, then break the tip of the suction tip 70 and drop it into the container. Thereby, according to the modified example and the applied example, it is possible to prevent the infiltration of the solution due to capillary action.

In addition, in the modified example/application example, the sample after suction can be stored stably by previously placing an organic solvent or a chemical agent that stops the enzymatic reaction in the container. For example, in the case of single-cell gene analysis, the control unit 30 controls the reaction temperature of reagents using a heat block in the sample collection unit. A heat block is a device that keeps the temperature constant. Thus, according to the modified example and application example, conversion of the obtained sample into cDNA and gene amplification can be performed within the apparatus. Note that cDNA (complementary DNA (complementary deoxyribonucleic acid)) is a double-stranded DNA synthesized from mRNA (messenger ribonucleic acid) by reverse transcription using a reverse transcriptase. As a result, according to the modified example, deterioration of the sample can be prevented, and a stable state can be achieved quickly.

In addition, in the modification/application example, after the cells are aspirated, the controller 30 moves the microplate 2 to a cell culture well plate 3 different from the aspirated cell culture well plate 3, and a small amount of the reagent is aspirated into the aspiration tip 70. It is possible to create a minute amount of reaction system by sucking from the tip of the. A reagent is put in another cell culture well plate 3 in advance.

The samples (specimens) collected in the embodiments, modifications, and applications can also be used for mass spectrometry, protein expression analysis, etc., in addition to gene analysis as subsequent analysis.

A program for realizing all or part of the functions of the control unit 30 in the present invention is recorded in a computer-readable recording medium, and the program recorded in this recording medium is read by a computer system and executed. Therefore, all or part of the processing performed by the control unit 30 may be performed. It should be noted that the "computer system" referred to here includes hardware such as an OS and peripheral devices. Also, the "computer system" includes a WWW system provided with a home page providing environment (or display environment). The term "computer-readable recording medium" refers to portable media such as flexible discs, magneto-optical discs, ROMs and CD-ROMs, and storage devices such as hard discs incorporated in computer systems. In addition, "computer-readable recording medium" means a volatile memory (RAM) inside a computer system that acts as a server or client when a program is transmitted via a network such as the Internet or a communication line such as a telephone line. , includes those that hold the program for a certain period of time.

Further, the above program may be transmitted from a computer system storing this program in a storage device or the like to another computer system via a transmission medium or by a transmission wave in a transmission medium. Here, the "transmission medium" for transmitting the program refers to a medium having a function of transmitting information, such as a network (communication network) such as the Internet or a communication line (communication line) such as a telephone line. Further, the program may be for realizing part of the functions described above. Further, it may be a so-called difference file (difference program) that can realize the above-described functions in combination with a program already recorded in the computer system.

As described above, the mode for carrying out the present invention has been described using the embodiments, but the present invention is not limited to such embodiments at all, and various modifications and replacements can be made without departing from the scope of the present invention. can be added.

DESCRIPTION OF SYMBOLS 1... Cell suction support apparatus, 2... Microplate, 3... Cell culture well plate, 4... Cell, 5... Cell culture solution, 41... Nucleus, 10... Image acquisition/analysis part, 20... Suction part, 30... Control part , 35 operation unit 40 image display unit 50 suction pressure setting unit 55 suction time setting unit 60 XYZ stage 70 suction tip 80 tip rack 90 sample rack 101 microscopic optics Unit 102 Confocal scanning unit 103 Imaging unit 104 Light source for fluorescence 105 Bright field illumination 106 XY stage 301 Reception unit 302 Image acquisition unit 303 Image processing unit 304 Storage unit 305 Operation control unit 306 Display control unit

Claims (9)

a tubular aspiration tip for aspirating a sample that is at least one of a tissue, a cell, and a portion of a cell contained in the container;
a suction unit that sucks the sample from the tip of the suction tip;
an imaging unit for imaging the sample;
Information about the height of the sample is detected by focusing on the maximum position in the height direction of the sample to be aspirated based on the image captured by the imaging unit, and the image captured by the imaging unit is captured. based on the information on the height direction of the tip of the suction tip is detected, and based on the detected information on the height of the sample and the information on the height direction of the tip of the suction tip, the suction tip for the sample a control unit that controls the sample to be aspirated by the aspiration tip after controlling the relative position in the height direction of the
A cell aspiration support device. The control unit
controlling the height of the aspiration tip to a position lower by a predetermined height than the maximum position in the height direction of the sample to be aspirated;
The cell aspiration support device according to claim 1 . The control unit detects information about the height of the sample for each suction start position at which suction is started in the sample or for each sample.
The cell suction support device according to claim 1 or 2 . When the control unit determines to continue the aspiration operation by capturing another image of the sample to be aspirated by the imaging unit, the control unit determines to continue the aspiration operation by capturing the image of the sample to be aspirated based on the image captured by the imaging unit. Information about the height of the sample is detected by focusing on a part, information about the height direction of the tip of the suction tip is detected based on the image captured by the imaging unit, and the detected sample After controlling the relative position of the suction tip in the height direction with respect to the sample based on information about the height of the tip of the suction tip and information about the height direction of the tip of the suction tip, the sample to be sucked by the suction tip Repeat the suction process to suck the
The control unit terminates the aspiration process when determining not to continue the aspiration work by imaging another image of the sample to be aspirated by the imaging unit.
The cell suction support device according to any one of claims 1 to 3 . The control unit
Based on the image captured by the photographing unit, control is performed so that the sample to be aspirated is aspirated by the aspiration tip in accordance with the information on the aspiration time and the information on the aspiration pressure corresponding to the sample to be aspirated. The cell aspiration support device according to claim 1. an operation unit for selecting whether to automatically or manually set conditions for aspirating the sample to be aspirated;
a suction time setting unit for setting a suction time by the suction tip;
a suction pressure setting unit for setting a suction pressure by the suction tip;
an image display unit that displays an image captured by the imaging unit;
with
The control unit
When manually setting conditions for aspirating the sample to be aspirated as a result of operating the operation unit, information indicating the aspiration time set by the aspiration time setting unit is obtained, and the aspiration pressure is set. acquires information indicating the aspiration pressure set by the unit, and controls the suction tip to aspirate the sample to be aspirated according to the acquired information indicating the aspiration time and the information indicating the aspiration pressure. do,
The cell suction support device according to any one of claims 1 to 5 . The control unit
7. The method according to claim 6 , wherein the information indicating the aspiration time set by the aspiration time setting unit and the information indicating the aspiration pressure set by the aspiration pressure setting unit are stored in association with the sample to be aspirated. The cell aspiration support device described. A cell aspiration support device having a tubular aspiration tip for aspirating a sample that is at least one of a tissue, a cell, and a part of a cell contained in a container, and a suction part for aspirating the sample from the tip of the aspiration tip. A control method of
an imaging procedure in which the imaging unit images the sample;
a sample height detection procedure in which the control unit detects information about the height of the sample by focusing on the maximum position in the height direction of the sample to be aspirated based on the image captured by the imaging unit; ,
a tip tip height detection procedure in which the control unit detects information about the height direction of the tip of the suction tip based on the image captured by the imaging unit;
A relative position control procedure in which the control unit controls the relative position of the suction tip in the height direction with respect to the sample based on the detected information about the height of the sample and the information about the height direction of the tip of the suction tip. and,
a control procedure in which the control unit causes the aspiration chip to aspirate the sample to be aspirated;
A control method for a cell aspiration support device including After aspirating the sample, including a procedure for determining whether to continue the aspiration work by taking another image,
When it is determined to continue the aspiration operation, the imaging procedure, the sample height detection procedure, the tip tip height detection procedure, the relative position control procedure, and the control procedure are performed for each aspiration start position at which aspiration is started, Alternatively, the method for controlling a cell aspiration assisting device according to claim 8 , comprising: a procedure performed for each sample.

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